Effects of Thymus revolutus Célak essential oil and its two major components on Hep G2 cells membrane

In this study pro/anti-oxidant activities of Thymus revolutus Célak (T. revolutus C.) essential oil and its two main components on Hep G2 cells were determined. Twelve components were identified in T. revolutus C. essential oil by GC and GC-MS and the main components of the oil were cymene (32.57%) and γ-terpinene (17.18%). The essential oil showed more cytotoxicity than its two main components on Hep G2 after 24, 48 and 72 hours incubations. Membrane damage effects of the essential oil and its two main components on Hep G2 cells were increased by incubation with IC₁₀, IC₅₀ and IC₇₀ concentrations. Lower essential oil (<IC₅₀) concentrations had cytoprotective and membrane protective effects against H₂O₂. The free radical scavenging activity of the essential oil of T. revolutus C. (EC₅₀ = 250±0.2 μg/mL) was superior to its two main components (neither not active). Oxidation of linoleic acid was effectively inhibited by T. revolutus C. (72.8%), while inhibition values of linoleic acid oxidation were calculated as 23.4.% and 26.7% for cymene and Γ-terpinene, respectively. These findings suggest that essential oils and its two main components had both pro-oxidant and protective (antioxidant) effects and they exhibited those effects depending on concentration.     

A comparative study of cytotoxic, membrane and DNA damaging effects of Origanum majorana’s essential oil and its oxygenated monoterpene component linalool on parental and epirubicin-resistant H1299 cells

In this study, cytotoxic, membrane and DNA damaging effects of the essential oil from Origanum majorana and its oxygenated monoterpene component linalool were tested on parental and epirubicin-resistant (drug-resistant) human lung cancer cell lines (H1299). Essential oil’s and linalool’s cytotoxicities were examined and parental cells were found more sensitive to the essential oil’s and linalool’s cytotoxicities than drug-resistant cells. O. majorana essential oil had more effective membrane damaging effect than linalool on parental cells, while in drug-resistant H1299 cells, linalool had more effective membrane damaging effect than the essential oil. O. majorana essential oil possessed more effective DNA damaging effect than linalool on both parental and drug-resistant cells. The conclusions from this study suggest that O. majorana essential oil and linalool exhibit cytotoxic, membrane and DNA damaging effects. They thus need further investigation as potential therapeutic agents for human lung cancer.     

New artesunic acid homodimers: Potent reversal agents of multidrug resistance in leukemia cells

To evade the problem of multidrug resistance, hybridization of natural products in dimers is considered as an effective method. After the successful synthesis of three artesunic acid homodimers connected by different types of chemical linkers, we analyzed their activity against human CCRF-CEM and multidrug-resistant p-glycoprotein-overexpressing CEM/ADR 5000 leukemia cells and observed, that multidrug resistant cells were not cross-resistant to the new compounds. Collateral sensitivity was observed for artesunic acid homodimer 2. The obtained results deliver valuable information about the linker's structure which is required for homodimers to be highly cytotoxic.     

Apolipoprotein A5 polymorphisms in Turkish population: association with serum lipid profile and risk of ischemic stroke

Atherosclerosis, a major cause of ischemic stroke, may be associated with variability of triglyceride (TG) levels. Apolipoprotein A5 (APOA5) genetic polymorphisms are associated with altered TG levels. The objective of this study was to investigate the coding region polymorphisms S19W (rs3135506) and G185C (rs2075291) and the promoter region polymorphism ?1131T>C (rs662799) of the APOA5 gene as risk factors for ischemic stroke in Turkish population. Study group consisted of 272 ischemic stroke patients and 123 controls. Genotypes were determined by real-time polymerase chain reaction (PCR) for S19W and PCR-restriction fragment length polymorphism analysis (PCR–RFLP) for ?1131T>C and G185C. 19W allele frequency was 0.090 in stroke patients and 0.062 in controls (P = 0.191). Minor allele frequencies of ?1131T>C and G185C in patients were 0.106 and 0.004, respectively, and were nearly the same in controls. Total cholesterol and LDL-cholesterol levels were significantly higher for stroke patients having at least one 19W allele compared to non-carriers. A significant difference was also found for LDL-cholesterol levels of stroke patients; higher in ?1131C allele carriers compared to wild type patients. There was a trend for higher frequency of ischemic stroke among ?1131C allele carrier hypertensive, diabetic or obese subjects compared to non-carriers. However, APOA5 genotypes were not associated with the risk of ischemic stroke by logistic regression analysis. The present study demonstrated that carrying rare alleles of APOA5 S19W, ?1131T>C and G185C alone do not constitute a risk for ischemic stroke in the studied Turkish subjects.     

Flow cytometry: basic principles and applications

Flow cytometry is a sophisticated instrument measuring multiple physical characteristics of a single cell such as size and granularity simultaneously as the cell flows in suspension through a measuring device. Its working depends on the light scattering features of the cells under investigation, which may be derived from dyes or monoclonal antibodies targeting either extracellular molecules located on the surface or intracellular molecules inside the cell. This approach makes flow cytometry a powerful tool for detailed analysis of complex populations in a short period of time. This review covers the general principles and selected applications of flow cytometry such as immunophenotyping of peripheral blood cells, analysis of apoptosis and detection of cytokines. Additionally, this report provides a basic understanding of flow cytometry technology essential for all users as well as the methods used to analyze and interpret the data. Moreover, recent progresses in flow cytometry have been discussed in order to give an opinion about the future importance of this technology.     

Interferon-alpha reduces the development of experimental necrotizing enterocolitis

Cytokines had important role in the pathogenesis of necrotizing enterocolitis (NEC). The aim of this study is to investigate if IFN-alpha has a prophylaxic effect on experimental NEC development in newborn rat pups. Twenty eight Wistar Albino newborn rat pups were divided into three groups. Control group rats were breast-fed, NEC group and interferon (IFN) group rat pups were hand-fed with premature newborn formula. IFN-alpha was administered subcutaneously at a dose of 50,000 IU/rat/day in IFN group. NEC was induced experimentally by cold stress twice a day in IFN and NEC groups. On the fourth day, the rats were killed, and all the intestine were removed to determine the tissue level of malonaldehyde (MDA) and histologic changes. The microscopic lesions in the NEC group rats were virtually the same as those seen in neonatal NEC, with severe separation of submucosa and/or lamina propria, loss of villi and in some cases necrosis to extention the muscularis. In contrast, in the rats treated with IFN, lesions were moderate separation of submucosa and/or lamina propria, edema in submucosal and muscular layers. Intestinal injury score and MDA levels in NEC group were significantly higher than in the IFN group (P<0.05). In conclusion it was suggested that IFN-alpha was effective in reducing the severity of NEC in rat pups.     

Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case–control study

Brain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) are neurotrophic factors that play key roles in the auditory pathway. While the relationship between serum levels and polymorphisms of BDNF/GDNF and chronic tinnitus is emphasized in the literature, there is no study showing the link between the promoter methylations of these genes and tinnitus. For this purpose, the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations was investigated to identify their role in the pathophysiology of tinnitus. In this case–control study, we examined the possible effects of BDNF/GDNF methylations in the blood samples of patients with tinnitus complaints for more than 3 months. Sixty tinnitus subjects between the ages of 18–55 and 50 healthy control subjects in the same age group who were free of any otorhinolaryngology and systemic disease were selected for examination. Methylation of total 12 CpG sites in BDNF and GDNF promoter regions were determined by the bisulfite-pyrosequencing method. Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5-6 methylation ratios in the comparison of control group and the chronic tinnitus patients (P?=?0.002, 0.0005, 0.00003, and 0.0029, respectively). To our knowledge, this is the first study in the literature investigating the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations. It is believed that the current results might be supported by investigating the relationships between BDNF/GDNF methylations and genotypes in future research using higher sample sizes.

     

Differential in vitro anti-leukemic activity of resveratrol combined with serine palmitoyltransferase inhibitor myriocin in FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) carrying AML cells

Cytotechnology - Treatment of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) AML is restricted due to toxicity, drug resistance and relapse eventhough targeted therapies are...     

Synthesis of new betulinic acid/betulin-derived dimers and hybrids with potent antimalarial and antiviral activities

Severe malaria and viral infections cause life-threatening diseases in millions of people worldwide every year. In search for effective bioactive hybrid molecules, which may possess improved properties compared to their parent compounds, a series of betulinic acid/betulin based dimer and hybrid compounds carrying ferrocene and/or artesunic acid moieties, was designed and, synthesized de novo. Furthermore, they were analyzed in vitro against malaria parasites (growth inhibition of 3D7-strain P. falciparum-infected erythrocytes) and human cytomegalovirus (HCMV). From this series of hybrids/dimers, the betulinic acid/betulin and artesunic acid hybrids 11 and 12 showed the most potent activities against P. falciparum and HCMV. On the strength of results, additive and/or synergistic effects between the natural or semisynthetic products, such as betulinic acid-/betulin- and artesunic acid-derived compounds, are suggested on the basis of putatively complex modes of antimicrobial action. This advantage may be taken into account in future drug development.